Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis

被引：56

作者：

Kobori, Takuro ^{[1
]}

Hamasaki, Shinichi ^{[2
]}

Kitaura, Atsuhiro ^{[2
]}

Yamazaki, Yui ^{[1
]}

Nishinaka, Takashi ^{[1
]}

Niwa, Atsuko ^{[1
]}

Nakao, Shinichi ^{[2
]}

Wake, Hidenori ^{[3
]}

Mori, Shuji ^{[4
]}

Yoshino, Tadashi ^{[5
]}

Nishibori, Masahiro ^{[3
]}

Takahashi, Hideo ^{[1
]}

机构：

[1] Kindai Univ, Dept Pharmacol, Fac Med, Osaka, Japan

[2] Kindai Univ, Dept Anesthesiol, Fac Med, Osaka, Japan

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmacol, Okayama, Japan

[4] Shujitsu Univ, Sch Pharm, Dept Pharmacol, Okayama, Japan

[5] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol, Okayama, Japan

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

基金：

日本学术振兴会;

关键词：

macrophage; CD163; angiogenesis; interleukin-18; osteopontin; thrombin; TUMOR-ASSOCIATED MACROPHAGES; RHEUMATOID-ARTHRITIS; SYNOVIAL TISSUE; OVARIAN-CANCER; M2-POLARIZED MACROPHAGES; ALPHA-9-BETA-1; INTEGRIN; MURINE MACROPHAGES; POTENTIAL ROLE; SOLUBLE CD163; UP-REGULATION;

D O I：

10.3389/fimmu.2018.00334

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

M2 macrophage (M phi) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 M phi s in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse M phi-like cell line, RAW264.7 cells, and mouse endothelial cell line, b.End5 cells. We discovered that IL-18 acts synergistically with IL-10 to amplify the production of M phi-derived mediators like osteopontin (OPN) and thrombin, yielding thrombin-cleaved form of OPN generation, which acts through integrins alpha 4/alpha 9, thereby augmenting M2 polarization of Mf with characteristics of increasing surface CD163 expression in association with morphological alteration. Furthermore, the results of visualizing temporal behavior and morphological alteration of Mfs during angiogenesis demonstrated that M2-like Mfs induced excessive angiogenesis through the direct cell-cell interaction with endothelial cells, possibly mediated by CD163.

引用

页数：20

共 100 条

[1] Interaction of Osteopontin with IL-18 in Obese Individuals: Implications for Insulin Resistance [J].